Loading
PDBj
MenuPDBj@FacebookPDBj@TwitterPDBj@YouTubewwPDB FoundationwwPDB
RCSB PDBPDBeBMRBAdv. SearchSearch help

8B8Q

Structure of mTMEM16F in lipid Nanodiscs in the presence of Ca2+

Summary for 8B8Q
Entry DOI10.2210/pdb8b8q/pdb
EMDB information15919 4611
DescriptorAnoctamin-6, CALCIUM ION (2 entities in total)
Functional Keywordsmembrane protein, lipid transport, lipid scramblase, ion channel, blood coagulation, membrane fusion
Biological sourceMus musculus (house mouse)
Total number of polymer chains2
Total formula weight227149.67
Authors
Arndt, M.,Alvadia, C.,Straub, M.S.,Clerico-Mosina, V.,Paulino, C.,Dutzler, R. (deposition date: 2022-10-04, release date: 2022-12-21)
Primary citationArndt, M.,Alvadia, C.,Straub, M.S.,Clerico Mosina, V.,Paulino, C.,Dutzler, R.
Structural basis for the activation of the lipid scramblase TMEM16F.
Nat Commun, 13:6692-6692, 2022
Cited by
PubMed Abstract: TMEM16F, a member of the conserved TMEM16 family, plays a central role in the initiation of blood coagulation and the fusion of trophoblasts. The protein mediates passive ion and lipid transport in response to an increase in intracellular Ca. However, the mechanism of how the protein facilitates both processes has remained elusive. Here we investigate the basis for TMEM16F activation. In a screen of residues lining the proposed site of conduction, we identify mutants with strongly activating phenotype. Structures of these mutants determined herein by cryo-electron microscopy show major rearrangements leading to the exposure of hydrophilic patches to the membrane, whose distortion facilitates lipid diffusion. The concomitant opening of a pore promotes ion conduction in the same protein conformation. Our work has revealed a mechanism that is distinct for this branch of the family and that will aid the development of a specific pharmacology for a promising drug target.
PubMed: 36335104
DOI: 10.1038/s41467-022-34497-x
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.94 Å)
Structure validation

226707

PDB entries from 2024-10-30

PDB statisticsPDBj update infoContact PDBjnumon